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Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

ABSTRACT: Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

SUBMITTER: Sandhu R

PROVIDER: S-EPMC4727830 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

Sandhu Rupninder R Chollet-Hinton Lynn L Kirk Erin L EL Midkiff Bentley B Troester Melissa A MA

Human pathology 20151023

Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonf ...[more]

PMID: 26772400

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Project description:IntroductionA postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women.MethodsAdjacent normal breast tissues from premenopausal women (n?=?183) aged 20 to 45 years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods.ResultsHuman nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12 months postpartum. By 18 months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame.ConclusionsHuman postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.

Project description:PurposeDrusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes.DesignLaboratory imaging and histologic comparison, and retrospective, observational cohort study.ParticipantsFour donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter.MethodsDonor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography.Main outcome measuresHistologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD.ResultsIntraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits.ConclusionsMultiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.

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Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

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Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

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